Dose-response relation, neuromuscular blocking action, intubation conditions, and cardiovascular effects of Org 9273, a new neuromuscular blocking agent

Abstract

The ED50 and the ED90, the time-course of the neuromuscular block, the intubation conditions, and the cardiovascular effects of Org 9273, a new steroidal nondepolarizing neuromuscular blocking agent, have been evaluated in 41 anesthetized patients. From cumulative dose-response curves the ED50 and ED90 were calculated to be 175 and 300 micrograms/kg, respectively. The time-course of neuromuscular blockade after 300- and 500-micrograms/kg doses of Org 9273 appeared to be similar to that of equipotent doses of vecuronium. The neuromuscular block was characterized by a fast initial rate of block development. High-dose Org 9273 (1 mg/kg = 3-4 times the ED90) had a clinical duration comparable to an intubating dose of pancuronium, but a considerably more rapid onset and recovery index. Three hundred micrograms per kilogram and 500 micrograms/kg Org 9273 produced good to excellent intubation conditions 1 min after administration. Org 9273 in a dose of 0.5-2 times the ED90 produced no cardiovascular changes; however, 3-4 times the ED90 increased heart rate 20%-25% (P less than 0.001), probably due to a vagolytic effect.